Studies were carried out to determine if the hydrolysis of phosphotidyl-inositol 4,5 bisphosphate (PIP2) is involved in transmitting an external stimulus into internal signals that result in the activation of B and T lymphocytes. Polyclonal activating agents (PAA) as well as lymphokines were used alone or in various combinations as agonist. Murine GO B cells induced by various PAA express IL-2 receptors when both translocation of protein kinase C and an increase in intracellular calcium ([Ca++]i) resulted from the activation process. However, B-cell proliferation induced by PAA did not require the expression of IL-2 receptors nor the hydrolysis of PIP2. Purified murine GO T-cells do not proliferate when cultured with phorbol myristate acetate (PMA) or calcium ionophores but actively proliferate when both substances were present in optimal amounts. PMA, but not ionophores, when combined with exogenous IL-2 induced the proliferation of GO T-cells. Neither PMA nor ionophore stimulation resulted in detectable levels of IL-2 but when added together to GO T-cells significant amounts of IL-2 were produced. Con A Stimulation of GO T-cells resulted in translocation of PK-c and an increase in [Ca++]i. These data suggest that activation of PK-c is an essential event in the expression of IL-2 receptors and that IL-2 production requires in addition an increase in intracellular CA++. T-cells from both humans and mice of different age show a reduced translocation of PK-c with advancing age which suggests a molecular basis for an age associated decline in T-cell function.